Academic medical centers (AMCs) are the nucleus of the U.S. health system, yet they face multiple challenges. Chief among these challenges are: the prospect of funding reductions with more than 10% of revenue under threat, new quality metrics that may weaken AMC’s market perception, and the structural inability to move quickly in a rapidly-changing environment. To survive, AMCs must reinvent themselves by embracing new types of collaboration, re-engineer operations, and use technology as a new kind of extender.